Intertwining nutrient‐sensory networks and the control of antibiotic production inStreptomyces

Abstract

Summary Actinobacteria are producers of a plethora of natural products of agricultural, biotechnological and clinical importance. In an era where mankind has to deal with rapidly spreading antimicrobial resistance, streptomycetes are of particular importance as producers of half of all antibiotics used in the clinic. Genome sequencing efforts revealed that their capacity as antibiotic producers has been underestimated, in particular as many biosynthetic pathways are silent under standard laboratory conditions. Here we review the global regulatory networks that control antibiotic production in streptomycetes, with emphasis on carbon‐ and aminosugar‐related nutrient sensory pathways. Recent research has revealed intriguing connections between these regulons, and overlap and antagonism between the activities of among others the global regulatory proteins AtrA, DasR and Rok7B7 as well as GlnR (nitrogen control) and PhoP (phosphate control), are discussed. Finally, we provide ideas as to how these novel insights might help us to find ways to activate the transcription of silent biosynthetic gene clusters.

Genome annotation and antimicrobial properties of Bacillus toyonensis VU‐DES13, isolated from the Folsomia candida gut

“…Previous reports showed that such signaling processes can be highly instrumental with regard to plant biocontrol and human gut health (Williams, ; Fischbach & Segre, ). Specific elicitors (environmental conditions and chemical triggers) have been described that can explain the highly conditional and specific expression of biosynthetic gene cluster for secondary metabolites (Niu et al., ; Urem et al., ). These findings imply a highly complex interplay between host, microbiome, and environment, taking into account many variables that we have only started to unravel.…”

Regulation of specialised metabolites in Actinobacteria – expanding the paradigms

“…For instance, DasR, a GntR‐like repressor, responds to environmental conditions by sensing the levels of the chitin monomer GlcNAc and integrates the regulation of primary metabolism, development and antibiotic production in Actinobacteria. The role of DasR in the genus Streptomyces has been recently reviewed in Urem and colleagues (). Inorganic phosphate starvation also triggers the production of several specialised metabolites in actinomycetes (Nieselt et al ., ; Allenby et al ., ; Martín et al ., ).…”

“…It is important to note that the above global physiological master regulators are subject to intricate cross‐regulatory metabolic networks, which have an effect on the production of specialised metabolites in actinomycetes as recently reviewed by Urem and colleagues ().…”

Role of GntR Family Regulatory GeneSCO1678in Gluconate Metabolism inStreptomyces coelicolorM145

“…Two of them, WhiH and DasR, have been extensively studied in the past. WhiH controls early steps of sporulation [10, 11], while DasR is a pleiotropic regulator of multiple carbohydrate transporters, chitin metabolism and antibiotic production genes [12]. A third regulator, Sco0823, was recently proposed by us to participate in ferric ion uptake [9].…”